Computer simulation of polymers in confined and crowded environments

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Polymers are chain-like molecules composed of a sequence of repeating chemical units called monomers. DNA is a biologically significant example of a polymer, one whose monomeric units are called nucleotides. It is the sequence of the nucleotides that comprises the genetic information of an organism. In recent years, there has been intense research activity devoted to the development of novel technologies for manipulating and analyzing DNA. Many of these technologies involve the transport of DNA through very compact regions of of space. The confinement of polymers in such regions is known to affect their physical properties. For example, the flexibility of polymers means that they will sample many different molecular shapes, or conformations, and confinement reduces the number of accessible conformations. Thus, the conformational "entropy" (a measure of the number of such conformations) decreases. Another quantity called "free energy" tends to increase as the entropy decreases. A basic understanding of the relationship between the free energy and the nature of the confinement of polymers is essential for interpreting the results of experiments involving confined DNA and thus for developing techniques for DNA analysis. In addition, this information is useful for understanding natural processes. One example is the segregation of replicated chromosomes (which are comprised of DNA) in bacteria. It is thought that the process may be driven in part by the natural tendency for the conformational free energy to decrease, and this is affected by the confinement inside the bacterium. In addition to confinement, the effects of "crowding" due to large proteins and other cellular components can also influence the dynamics of other processes involving DNA and other biopolymers. ***I will use computer simulation methods to study the effects of confinement and crowding on the free energy of polymers. A simulation is a virtual experiment on a model system carried out on a computer. Simulations can be used to interpret the results of experiments and test the validity of theoretical descriptions of experimental systems. I will use simple molecular models (to make the calculations feasible) to study polymers in a variety of confinement conditions corresponding to those used in DNA experiments. I will also study polymer separation under confinement conditions similar to those inside bacteria, as well as investigate the effects of macromolecular crowding. The simulations will be used mainly to explicitly calculate the conformational free energy using a variety efficient methods. These results of the calculations will be useful for (1) developing better theories for confined polymers, (2) understanding observations in confined-DNA experiments, (3) guiding the development of DNA analysis methods, and (4) better understanding cellular processes involving biopolymers such as DNA.**